Glimepiride - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 79.30 mg, microcrystalline cellulose - 12.00 mg, sodium carboxymethyl starch - 4.00 mg, povidone-K25 - 2,50 mg, polysorbate-80 - 0.50 mg, magnesium stearate - 0.70 mg.

One tablet of 2.0 mg contains:

Active substance: glimepiride - 2.00 mg;

Excipients: lactose monohydrate (sugar milk) - 78.30 mg, microcrystalline cellulose - 12.00 mg, sodium carboxymethyl starch - 4.00 mg, povidone-K25 - 2,50 mg, polysorbate-80 - 0.50 mg, magnesium stearate - 0.70 mg.

One 3.0 mg tablet contains:

Active substance: glimepiride - 3.00 mg;

Excipients: lactose monohydrate (sugar milk) - 117.45 mg, microcrystalline cellulose - 18.00 mg, sodium carboxymethyl starch - 6.00 mg, povidone-K25 - 3.75 mg, polysorbate-80 - 0.75 mg, magnesium stearate - 1 , 05 mg.

One tablet of 4.0 mg contains:

Active substance: glimepiride - 4,00 mg;

Excipients: lactose monohydrate (sugar milk) - 156,60 mg, microcrystalline cellulose - 24,00 mg, sodium carboxymethyl starch - 8,00 mg, povidone-K25 - 5,00 mg, polysorbate-80 - 1,00 mg, magnesium stearate - 1 , 40 mg.

Description:Tabhetki white or almost white color: dosage of 1 mg - round, biconcave, with a risk, on the one hand; dosages of 2 mg, 3 mg, 4 mg - round, flat-cylindrical, with a risk, on the one hand and chamfers.

Pharmacotherapeutic group:Hypoglycemic agent for oral use of the sulfonylurea group of the third generation

ATX: & nbsp

A.10.B.B.12 Glimepiride

Pharmacodynamics:

Glimepiride reduces the concentration of glucose in the blood, mainly by stimulating the release of insulin from the beta cells of the pancreas. Its effect is mainly associated with improving the ability of beta cells of the pancreas to respond to physiological stimulation with glucose.

Compared to glibenclamide, taking low doses of glimepiride causes the release of less insulin when the blood glucose concentration is approximately the same. This fact testifies in favor of the presence in glimepiride of extrapancreatic hypoglycemic effects (increase of sensitivity of tissues to insulin and insulinomimetic effect).

Secretion of insulin. Like all other sulfonylureas, glimepiride regulates the secretion of insulin through interaction with ATP-sensitive potassium channels on the membranes of beta cells.Unlike other derivatives of sulfonylurea, glimepiride selectively binds to a protein with a molecular mass of 65 kDa, located in the membranes of beta cells of the pancreas. This interaction of glimepiride with the protein binding it regulates the opening or closing of ATP-sensitive potassium channels.

Glimepiride covers potassium channels. This causes depolarization of beta cells and leads to the discovery of voltage-sensitive calcium channels and the intake of calcium into the cell. As a result, an increase in the intracellular calcium concentration activates the secretion of insulin by exocytosis.

Glimepiride is much faster and, accordingly, more often enters into a bond and is released from the bond with the protein that binds it, than glibenclamide. It is suggested that this property of a high rate of exchange of glimepiride with the protein binding to it causes its pronounced effect of sensitizing beta cells to glucose and their protection against desensitization and premature exhaustion.

The effect of increasing the sensitivity of tissues to insulin. Glimepiride enhances insulin effects on glucose uptake by peripheral tissues.

Insulinomimetic effect. Glimepiride has effects similar to insulin effects on glucose uptake by peripheral tissues and glucose output from the liver. Absorption of glucose by peripheral tissues is carried out by its transport inside the muscle cells and adipocytes. Glimepiride directly increases the amount of glucose-transporting molecules in the plasma membrane of muscle cells and adipocytes. Increasing the intake of glucose into the cells leads to the activation of glycosylphosphatidylinositol-specific phospholipase C. As a result, the intracellular calcium concentration decreases, causing a decrease in the activity of protein kinase A, which in turn leads to stimulation of glucose metabolism.

Glimepiride inhibits glucose output from the liver by increasing the concentration of fructose-2,6-bisphosphate, which inhibits gluconeogenesis.

Effect on platelet aggregation. Glimepiride reduces platelet aggregation in vitro and in vivo. This effect appears to be due to the selective inhibition of cyclooxygenase, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor.

Antiatherogenic action of the drug. Glimepiride promotes normalization of lipid content, reduces the content of malonic aldehyde in the blood, which leads to a significant decrease in lipid peroxidation. In animals glimepiride leads to a significant decrease in the formation of atherosclerotic plaques.

Reducing the severity of oxidative stress, which is constantly present in patients with type 2 diabetes mellitus. Glimepiride increases the content of endogenous α-tocopherol, the activity of catalase, glutathione peroxidase and superoxide dismutase.

Cardiovascular Effects. Through ATP-sensitive potassium channels (see above) sulfonylureas derivatives also have an effect on the cardiovascular system. Compared with the traditional derivatives of sulfonylurea, glimepiride has a significantly lesser effect on the cardiovascular system, which can be explained by the specific nature of its interaction with the ATP-sensitive protein of the potassium channel binding to it.

In healthy volunteers, the minimum effective dose of glimepiride is 0.6 mg.

The effect of glimepiride is dose-dependent and reproducible.Physiological response to physical activity (reduced secretion of insulin) with the intake of glimepiride is preserved.

There are no significant differences in the effect, depending on whether the drug was taken 30 minutes before meals or just before meals. In patients with diabetes mellitus, sufficient metabolic control can be achieved within 24 hours with a single administration of the drug. In a clinical study, sufficient metabolic control was also achieved in 12 of 16 patients with renal insufficiency (creatinine clearance 4-79 ml / min).

Combined therapy with metformin. In patients with insufficient metabolic control with the maximum dose of glimepiride, combined therapy with glimepiride and metformin may be initiated. In two studies, combined therapy showed improved metabolic control compared with that in the treatment of each of these drugs individually. Combination therapy with insulin.

In patients with insufficient metabolic control, simultaneous insulin therapy can be initiated with the maximum doses of glimepiride.Based on the results of two studies, this combination achieves the same improvement in metabolic control as with only one insulin; however, combined therapy requires a lower dose of insulin.

Application the children. There is insufficient data on the long-term efficacy and safety of the drug in children.

Pharmacokinetics:

Absorption

With repeated administration of glimepiride in a daily dose of 4 mg, the maximum concentration (C_max) in the blood plasma is reached after about 2.5 hours and is 309 ng / ml. There is a linear relationship between dose and C_max glimepiride in blood plasma, as well as between the dose and the area under the concentration-time curve (AUC). When ingested glimepiride, its absolute bioavailability is complete. Eating does not have a significant effect on absorption, except for a slight slowing of its speed.

Distribution

For glimepiride characterized by a very low volume of distribution (about 8.8 liters) approximately equal to the albumin distribution volume, a high degree of binding to plasma proteins (99%) and low clearance (about 48 ml / min).

Metabolism

Glimepiride is metabolized in the liver (mainly with the participation of isoenzyme CYP2C9) with the formation of two metabolites - hydroxylated and carboxylated derivatives, which are found in urine and in feces.

Excretion

After a single glimepiride intake, 58% of the dose is excreted by the kidneys and 35% by the intestine. Unchanged glimepiride in the urine is not found.

The mean half-life (T_1/2), determined by serum concentrations under repeated administration, is approximately 5-8 hours. After taking high doses, there is a slight increase in T_1/2.

Average T_1/2hydroxylated and carboxylated metabolites of glimepiride is 3-5 and 5-6 hours, respectively.

Glimepiride penetrates into breast milk and through the placental barrier.

Comparison of single and multiple (once a day) glimepiride did not reveal significant differences in pharmacokinetic parameters; there is a very low variability between different patients. There is no significant accumulation of the drug.

Pharmacokinetics in special clinical cases

Pharmacokinetic parameters are similar in patients of different sex and different age groups.

In patients with impaired renal function (with low creatinine clearance), there is a tendency to increase the clearance of glimepiride and reduce its mean serum concentrations, which is likely due to a faster release of the drug due to its lower binding to the protein. Thus, in this category of patients there is no additional risk of cumulation of the drug.

Indications:

Diabetes mellitus type 2 (in monotherapy or as part of combination therapy with metformin or insulin).

Contraindications:

- Type 1 diabetes mellitus;

- diabetic ketoacidosis, diabetic precoma and coma;

- severe liver dysfunction (lack of clinical experience);

- severe renal dysfunction, incl. in patients on hemodialysis (lack of clinical experience);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- pregnancy;

- breast-feeding;

- children's age till 18 years;

- increased sensitivity to glimepiride or to any inactive component of the drug, to other derivatives of sulfonylurea or to sulfonamide preparations (risk of developing hypersensitivity reactions).

Carefully:

- In the first weeks of treatment (increased risk of developing hypoglycemia).

- In the presence of risk factors for the development of hypoglycemia (see section "Special instructions", it may be necessary to adjust the dose of glimepiride or the whole therapy).

- With intercurrent illnesses during treatment or when changing the lifestyle of patients (changing diet and eating time, increasing or decreasing physical activity).

- With insufficiency of glucose-6-phosphate dehydrogenase.

- In violation of absorption of food and drugs in the gastrointestinal tract (GIT) (intestinal obstruction, paresis of the intestine).

Pregnancy and lactation:

Glimepiride is contraindicated in pregnant women. In the case of a planned pregnancy or at the onset of pregnancy, a woman should be transferred to insulin therapy.

Glimepiride penetrates into breast milk, so it can not be taken during breastfeeding. In this case, you need to switch to insulin therapy or stop breastfeeding.

Dosing and Administration:

Tablets of the drug Glimepiride taken inside, whole, not liquid, squeezed a sufficient amount of liquid (about 0.5 cup).If necessary, the tablets can be divided along the risks into two equal parts.

Typically, the dose of the drug Glimepiride is determined by the target concentration of glucose in the blood. The lowest dose, sufficient to achieve the necessary metabolic control, should be used.

During treatment with the drug Glimepiride it is necessary to regularly determine the concentration of glucose in the blood. In addition, regular monitoring of glycated hemoglobin is recommended.

Incorrect drug intake, for example, skipping the next dose, should never be replenished by the subsequent administration of a higher dose.

The patient's actions in case of mistakes in taking the medication (in particular, if the next dose is skipped or the meal is skipped) or in situations where there is no possibility to take the drug, should be discussed by the patient and the doctor in advance.

Initial dose and dose selection

The initial dose is 1 mg glimepiride 1 time per day.

If necessary, the daily dose can be increased gradually (at intervals of 1-2 weeks). It is recommended that the dose be increased under regular control of blood glucose concentrations and in accordance with the following dose increment step: 1 mg-2 mg-3 mg-4 mg-6 mg- (8 mg).

Range of doses the patients with well-controlled diabetes mellitus

Usually a daily dose in patients with well-controlled diabetes mellitus is 1-4 mg of glimepiride. A daily dose of more than 6 mg is more effective only in a small number of patients.

Dosing regimen

The time of taking the drug and the distribution of doses during the day is determined by the doctor depending on the lifestyle of the patient at a given time (meal time, amount of physical exertion).

It is usually enough to take a single dose of the drug during the day. It is recommended that in this case the entire dose of the drug be taken immediately before a full breakfast or, if it was not taken at this time, just before the first main meal. It is very important after taking the tablets not to skip meals.

Since improvement in metabolic control is associated with an increase in insulin sensitivity, the need for glimepiride may decrease during treatment. In order to avoid the development of hypoglycemia, it is necessary to reduce the dose in a timely manner or stop taking the drug Glimepiride.

Conditions in which a dose adjustment may also be required:

- decreased body weight;

- changes in lifestyle (changing diet, meal time, amount of exercise);

- the occurrence of other factors that lead to a predisposition to the development of hypoglycemia or hyperglycemia (see section "Special instructions").

Duration of treatment

Treatment with drug Glimepiride it usually takes a long time.

Transfer of a patient from another hypoglycemic agent for oral administration to Glimepiride

There is no exact relationship between the doses of the drug Glimepiride and other hypoglycemic agents for oral administration. When another hypoglycemic agent for oral use is substituted for the drug Glimepiride, it is recommended that its initial dose be the same as for the initial prescription of the drug Glimepiridei.e. treatment should begin with a low dose of 1 mg (even if the patient is transferred to a drug Glimepiride with a maximum dose of another hypoglycemic preparation for oral administration).Any increase in the dose should be carried out in stages, taking into account the effectiveness of glimepiride in accordance with the recommendations given above.

It is necessary to take into account the strength and duration of the effect of the precursor hypoglycemic agent for oral administration. An interruption in treatment may be required in order to avoid any "summation of effects that may increase the risk of developing hypoglycemia."

Use in combination with metformin

In patients with insufficiently controlled diabetes mellitus, when taking the maximum daily doses of glimepiride or metformin, treatment with a combination of these two drugs can be started. In this case, the previous treatment with glimepiride or metformin continues at the same dose level, and an additional intake of metformin or glimepiride starts at a low dose, which is then titrated, depending on the target level of metabolic control, up to the maximum daily dose. Combination therapy should begin under strict medical supervision.

Use in combination with insulin

Patients with insufficiently controlled diabetes mellitus at intake of the maximum daily doses of glimepiride can simultaneously be prescribed insulin administration.In this case, the last dose of glimepiride prescribed to the patient remains unchanged. In this case, treatment with insulin begins with low doses, which gradually increase under the control of the concentration of glucose in the blood. Combined treatment requires careful medical supervision.

Application the patients with renal insufficiency

There is a limited amount of information on the use of glimepiride in patients with renal insufficiency. Patients with impaired renal function may be more sensitive to the hypoglycemic effect of glimepiride (see the sections "Pharmacokinetics", "Contraindications").

Application the patients with hepatic insufficiency

There is a limited amount of information on the use of glimepiride in liver failure (see "Contraindications").

Application the children

Data on the use of the drug in children is not enough.

Side effects:

From the side of metabolism: as a result of hypoglycemic action of the drug may develop hypoglycemia, which, like with other derivatives of sulfonylureas, can be prolonged.

Symptoms of hypoglycemia are: headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbance, anxiety, aggressiveness, impaired concentration, alertness and reaction speed, depression, confusion, speech disorders, aphasia, visual disturbances, tremor, paresis, sensory dizziness, loss of self-control, delirium, cerebral cramps, doubt or loss of consciousness, including coma, shallow breathing, bradycardia.

In addition, there may occur adrenergic counterregulation in response to hypoglycemia, such as the appearance of cold sticky sweat, anxiety, tachycardia, increased blood pressure (BP), angina pectoris, palpitations and heart rhythm disturbances.

The clinical picture of severe hypoglycemia may be similar to a stroke. Symptoms of hypoglycemia almost always disappear after its elimination.

From the side of the organ of vision: during treatment (especially at the beginning), transient visual impairments due to changes in the concentration of glucose in the blood can be observed. Their cause is a temporary change in the swelling of the lens, depending on the concentration of glucose in the blood, and due to this - a change in the refractive index of the lens.

From the gastrointestinal tract: in rare cases - nausea, vomiting, a feeling of heaviness or overflow in the epigastrium, abdominal pain, diarrhea.

In some cases - hepatitis, increased activity of "liver" enzymes and / or cholestasis and jaundice, which can progress to life-threatening liver failure, but may undergo reverse development if the drug is withdrawn.

On the part of the blood and lymphatic system: rarely - thrombocytopenia.

In some cases - leukopenia, hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia.

In post-marketing applications of the drug reported cases of severe thrombocytopenia with a platelet count of less than 10,000 / μL and thrombocytopenic purpura (frequency unknown).

Immune system disorders: In rare cases, allergic and pseudo-allergic reactions, such as pruritus, hives, skin rashes, are possible. Such reactions almost always have an easy form, but they can turn into severe reactions with shortness of breath, a sharp decrease in blood pressure, which sometimes progresses down to anaphylactic shock. When symptoms of urticaria appear, consult a doctor immediately.

General disorders and disorders at the site of administration: in some cases, there may be a decrease in the concentration of sodium in the blood plasma, allergic vasculitis, photosensitivity.

Overdose:

Symptoms: Acute overdose, as well as long-term treatment with too high doses of glimepiride, can lead to the development of severe life-threatening hypoglycemia.

Treatment: As soon as an overdose is discovered, the doctor must be informed immediately. Hypoglycemia can almost always be quickly stopped by the immediate intake of carbohydrates (glucose or a piece of sugar, sweet fruit juice or tea). In this regard, the patient should always have at least 20 grams of glucose (4 pieces of sugar). Sugary substitutes are ineffective in the treatment of hypoglycemia.

Until the doctor decides that the patient is out of danger, careful medical supervision of the patient is necessary. Hypoglycemia can resume after initial recovery of blood glucose.

If a patient with diabetes is treated by different doctors (for example, during a hospital stay after an accident, with a disease on a weekend), he must necessarily inform them about his illness and previous treatment.

Sometimes the patient may need to be hospitalized, even if only as a precaution. Significant overdose and severe reactions with such manifestations as loss of consciousness or other serious neurological disorders are urgent medical conditions and require immediate treatment and hospitalization.

In the unconscious state of the patient, an intravenous (iv) concentrated dextrose (glucose) solution is necessary (in adults, starting with 40 ml of a 20% solution). As an alternative to adults, IV, subcutaneous or intramuscular glucagon administration, for example at a dose of 0.5-1 mg, is possible.

In the treatment of hypoglycemia due to accidental intake of the drug by infants or young children, the dose of dextrose administered should be carefully adjusted in terms of the possibility of dangerous hyperglycemia, and the administration of dextrose should be carried out under constant control of the glucose concentration in the blood.

In case of glimeperid overdose, it may be necessary to perform gastric lavage and receive activated charcoal.

After a rapid recovery of the concentration of glucose in the blood, an IV infusiondextrose solution at a lower concentration to prevent the resumption of hypoglycemia. The concentration of blood glucose in these patients should be constantly monitored within 24 hours. In severe cases with prolonged course of hypoglycemia, the risk of reducing the glucose concentration in the blood to the hypoglycemic level may persist for several days.

Interaction:

Glimepiride is metabolized by cytochrome P4502C9 (CYP2C9), which should be taken into account when it is used simultaneously with inductors (for example, rifampicin) or inhibitors (e.g., fluconazole) CYP2C9.

Potentiation of hypoglycemic action and in some cases associated with this possible development of hypoglycemia may be observed when combined with one of the following drugs: insulin and other hypoglycemic agents for oral use, angiotensin converting enzyme (ACE) inhibitors, anabolic steroids and male sex hormones, chloramphenicol. derivatives of coumarin, cyclophosphamide, disopyramide, fenfluramine, pheniramidol, fibrates, fluoxetine, guanethidine, ifosfamide, monoamine oxidase inhibitors, fluconazole, para- aminosalicylic acid, pentoxifylline (high parenteral doses), phenylbutazone, azapropazon, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, clarithromycin, sulfonamides, tetracyclines, tritokvaline, trophosfamide.

The weakening of hypoglycemic action and the associated increase in the concentration of glucose in the blood can be observed when combined with one of the following drugs: acetazolamide, barbiturates, glucocorticosteroids, diazoxide, diuretics, epinephrine and other sympathomimetic agents, glucagon, laxatives (with prolonged use), a nicotinic acid (in high doses), estrogens and progestogens, phenothiazines, phenytoin, rifampicin, iodine-containing hormones of the thyroid gland.

Blockers H₂-gistaminovyh receptors, beta-adrenoblockers, clonidine and reserpine are able both to intensify, and to weaken the hypoglycemic action of glimepiride.

Under the influence of sympatholytic agents, such as beta-blockers, clonidine, guanethidine and reserpine, signs of adrenergic counterregulation in response to hypoglycemia may decrease or be absent.

Against the background of taking glimepiride, there may be an increase or decrease in the action of coumarin derivatives.

Single or chronic alcohol use can, both enhance and weaken the hypoglycemic effect of glimepiride.

Sequestants of bile acids: kosevelam binds with glimepiride and reduces the absorption of glimepiride from the digestive tract. In the case of using glimepiride at least 4 hours before the administration of colevevelam, no interaction is observed. therefore glimepiride must be taken at least 4 hours prior to the intake of Wheezevelum.

Special instructions:

In special clinical stress conditions such as trauma, surgery, infection with febrile temperature, metabolic control may worsen in patients with diabetes mellitus, and they may need a temporary transfer to insulin therapy to maintain adequate metabolic control.

In the first weeks of treatment, the risk of developing hypoglycemia may increase, and therefore at this time a particularly careful control of the concentration of glucose in the blood is required.

Factors that contribute to the risk of developing hypoglycemia include:

- unwillingness or inability of the patient (most often observed in elderly patients) to cooperate with a doctor;

- malnutrition, irregular eating or skipping meals;

- an imbalance between exercise and carbohydrate intake;

- changing diet;

- alcohol consumption, especially when combined with meals;

- severe renal dysfunction;

- severe violations of liver function (in patients with severe impairment of liver function, a transfer to insulin therapy is indicated, at least until metabolic control is achieved);

- an overdose of glimepiride;

- some decompensated endocrine disorders that disrupt carbohydrate metabolism or adrenergic counterregulation in response to hypoglycemia (for example, certain disorders of the thyroid gland and anterior pituitary gland, insufficiency of the adrenal cortex);

- simultaneous intake of certain medicines (see section "Interaction with other drugs");

- reception glimepirida in the absence of indications for its use.

Treatment with derivatives of sulfonylurea, which includes glimepiride, can lead to the development of hemolytic anemia, therefore, patients with glucose-6-phosphate dehydrogenase deficiency should be especially careful in the appointment of glimepiride and it is better to use hypoglycemic agents that are not derivatives of sulfonylurea.

In case of presence of the above-listed risk factors for the development of hypoglycemia, a dose adjustment of glimepiride or the whole therapy may be required. This also applies to the occurrence of intercurrent illnesses during treatment or a change in the lifestyle of patients.

Symptoms of hypoglycemia, which reflect adrenergic counter-regulation of the body in response to hypoglycemia (see section "Side effect"), may be mild or absent with gradual development of hypoglycemia, in elderly patients, patients with neuropathy of the autonomic nervous system or patients receiving beta - adrenoblockers, clonidine, reserpine, guanethidine and other sympatholytic agents.

Hypoglycemia can be quickly eliminated by immediate intake of rapidly digesting carbohydrates (glucose or sucrose).

As with the administration of other sulfonylureas, despite initial successful reduction of hypoglycemia, hypoglycemia may resume. Therefore, patients should remain under constant supervision.

In severe hypoglycemia, immediate treatment and supervision of the physician, and in some cases, hospitalization of the patient, are required.

During treatment with glimepiride, regular monitoring of liver function and peripheral blood pattern (especially the number of leukocytes and platelets) is required.

Since certain side effects, such as severe hypoglycemia, severe changes in the blood picture, severe allergic reactions, liver failure, can under certain circumstances pose a life threat, in the event of unwanted or severe reactions, the patient should immediately be notified of the treating doctor and neither In any case, do not continue taking the drug without his recommendation.

Effect on the ability to drive transp. cf. and fur:

In the case of hypoglycemia or hyperglycaemia, especially at the beginning of treatment or after treatment change, or when the drug is not taken regularly, the attention and speed of psychomotor reactions may decrease.This can disrupt the patient's ability to drive vehicles or other mechanisms.

Form release / dosage:

Tablets, 1 mg, 2 mg, 3 mg and 4 mg.

Packaging:

For 10, 25, 30 or 50 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or 120 tablets in cans of polyethylene terephthalate for medicinal products sealed with screw caps with a first opening control or a "push-turn" system of polypropylene or polyethylene or polypropylene cans for medicines, capped with lids pullable with the control of the first opening of polyethylene or cans of polypropylene for medicines, capped with caps tightened with the control of the first opening of high pressure polyethylene.

One jar or 1, 2, 3, 4, 6, 9 or 12 contour squares, together with the instructions for use, are placed in a cardboard package (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003488

Date of registration:04.03.2016

Expiration Date:04.03.2021

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp30.04.2017

Illustrated instructions

Instructions

Glimepiride (Glimepiride)